A5070792652- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Liver Disease Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Lipid metabolism and biosynthesis
- Drug Transport and Resistance Mechanisms
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Lipoproteins and Cardiovascular Health
- Diet, Metabolism, and Disease
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and disorders
- Protein Kinase Regulation and GTPase Signaling
- MicroRNA in disease regulation
- Alcohol Consumption and Health Effects
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Fatty Acid Research and Health
- Biotin and Related Studies
- Cancer-related Molecular Pathways
Inha University
2016-2025
The University of Texas Southwestern Medical Center
2001-2017
Yonsei University
1994-2002
Howard Hughes Medical Institute
2001
PCSK9 encodes proprotein convertase subtilisin/kexin type 9a (PCSK9), a member of the proteinase K subfamily subtilases. Missense mutations in cause an autosomal dominant form hypercholesterolemia humans, likely due to gain-of-function mechanism because overexpression either WT or mutant reduces hepatic LDL receptor protein (LDLR) mice. Here, we show that livers knockout mice lacking manifest increased LDLR but not mRNA. Increased led clearance circulating lipoproteins and decreased plasma...
In liver, the synthesis of cholesterol and fatty acids increases in response to deprivation insulin elevation, respectively. This regulatory mechanism underlies adaptation inhibitors (statins) high calorie diets (insulin). nonhepatic cells, lipid is controlled by sterol element-binding proteins (SREBPs), membrane-bound transcription factors whose active domains are released proteolytically enter nucleus activate genes involved uptake acids. SCAP (SREBP cleavage-activating protein) a...
Site-1 protease (S1P) cleaves membrane-bound sterol regulatory element-binding proteins (SREBPs), allowing their transcription-stimulating domains to translocate the nucleus where they activate genes governing lipid synthesis. S1P is a potential target for lipid-lowering drugs, but effect of blockade in animals unknown. Here, we disrupt gene mice. Homozygous germ-line disruptions were embryonically lethal. To inducibly liver, generated mice homozygous floxed allele and heterozygous transgene...
The <i>de novo</i> synthesis of fatty acids occurs in two distinct cellular compartments. Palmitate (16:0) is synthesized from acetyl-CoA and malonyl-CoA the cytoplasm by enzymes carboxylase 1 acid synthase. longer than 16 carbons takes place microsomes utilizes as carbon source. Each two-carbon addition requires four sequential reactions: condensation, reduction, dehydration, a final reduction to form elongated acyl-CoA. initial condensation reaction regulated rate-controlling step...
Acetyl-CoA carboxylase (ACC), the first committed enzyme in fatty acid (FA) synthesis, is regulated by phosphorylation/dephosphorylation, transcription, and an unusual mechanism of protein polymerization. Polymerization ACC increases enzymatic activity induced vitro supraphysiological concentrations citrate (> 5 mM). Here, we show that MIG12, a 22 kDa cytosolic previously unknown function, binds to lowers threshold for activation into physiological range (< 1 In vitro, recombinant...
The synthesis of cholesterol and fatty acids (FA) in the liver is independently regulated by SREBP-2 SREBP-1c, respectively. Here, we genetically deleted Srebf-2 from hepatocytes confirmed that regulates all genes involved biosynthesis, LDL receptor, PCSK9; a secreted protein degrades receptors liver. Surprisingly, found elimination mice also markedly reduced SREBP-1c expression FA triglyceride are normally SREBP-1c. nuclear receptor LXR necessary for Srebf-1c transcription. deletion...
The lack of an appropriate preclinical model metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole spectrum impedes exploration pathophysiology and development effective treatment strategies. Here, we develop a mouse (Streptozotocin with high-fat diet, STZ + HFD) gradually develops fatty liver, steatohepatitis (MASH), hepatic fibrosis, hepatocellular carcinoma (HCC) in context dysfunction. transcriptomic features HFD mice closely reflect those patients...
Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine neurotransmitter that has various functions in central and peripheral tissues. While 5-HT known to regulate biological processes liver, direct role of its receptors, especially receptor 2A (HTR2A) HTR2B, development progression alcoholic liver disease (ALD) vivo not well understood. Blood level was measured from both human ALD patients ethanol (EtOH) diet-fed mouse models. Gut-specific tryptophan hydroxylase 1 (Tph1) knockout mice,...
A small molecule specifically kills cancer cells with APC truncations and spares wild-type APC.
Elongation of very long chain fatty acid-like family member 6 (ELOVL6) is a acyl elongase that performs the initial and rate-limiting condensing reaction required for microsomal elongation long-chain acids. Our previous in vitro studies suggested ELOVL6 elongated saturated acids monounsaturated with lengths 12 to 16 carbons. Here, we describe generation phenotypic characterization Elovl6(-/-) mice. As predicted from studies, livers mice accumulated palmitic (C16:0) palmitoleic (C16:1, n-7)...
The tumor microenvironment comprises both and non-tumor stromal cells, including tumor-associated macrophages (TAMs), endothelial carcinoma-associated fibroblasts. TAMs, major components of play a crucial role in creating an immunosuppressive environment by releasing cytokines, chemokines, growth factors, immune checkpoint proteins that inhibit T cell activity. During tumors develop, cancer cells release various mediators, chemokines metabolites, recruit monocytes to infiltrate tissues...
Spot 14 (S14) is a protein that abundantly expressed in lipogenic tissues and regulated manner similar to other enzymes involved fatty acid synthesis. Deletion of S14 mice decreased lipid synthesis lactating mammary tissue, but the mechanism S14’s action unknown. Here we present crystal structure 2.65 Å biochemical data showing can form heterodimers with MIG12. MIG12 modulates by inducing polymerization activity acetyl-CoA carboxylase, first committed enzymatic reaction pathway. Coexpression...
Liver fibrosis is a consequence of chronic liver injury associated with viral infection, alcohol abuse, and nonalcoholic fatty liver. The evidence from clinical animal studies indicates that transforming growth factor-β (TGF-β) signaling the development fibrosis. Krüppel-like factor 10 (KLF10) transcription plays significant role in TGF-β-mediated cell growth, apoptosis, differentiation. In recent studies, it has been reported to be glucose homeostasis insulin resistance. present study, we...
Abstract Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis fatty acyl-CoAs to free acids and CoA-SH. However, canonical non-canonical functions ACOT7 remain be discovered. In this study, for first time, was shown responsive genotoxic stresses such as ionizing radiation (IR) anti-cancer drug doxorubicin in time- dose-dependent manners. knockdown induced cytostasis via activation p53–p21 signaling pathway without DNA damage response. PKC ζ...
Peroxisome-proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein (SREBP) play a role in regulating cellular fatty acid cholesterol homeostasis via oxidation lipogenesis. The control of SREBP processing is regulated by the insulin induced gene (INSIG)2a protein, which binds to prevent translocation Golgi apparatus during nutrient starvation liver. However, regulation SREBP-1c INSIGs fasting mechanisms mouse Insig2a expression have not been clearly...
Polyunsaturated fatty acids (PUFAs) have important functions in biological systems. The beneficial effects of dietary PUFAs against inflammatory diseases, cardiovascular and metabolic disorders been shown. Studies using cancer cells presented the anti-tumorigenic docosahexaenoic acid (DHA), an n-3 PUFA, while arachidonic (AA), n-6 has shown to elicit both pro- effects. In current study, AA were evaluated HT-29 human colon cells. Upon adding media, more than 90% died, MCF7 showed good...
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